Molecular causes for life-threatening fungal infections in case of sepsis unravelled

Molecular causes for life-threatening fungal infections in case of sepsis unravelled

(Medical Xpress) -- Pathogenic fungi cause infections with a high mortality rate in patients with weakened immune systems. At Karl Kuchler’s CD Laboratory at the MedUni Vienna, the molecular causes of the life-threatening inflammatory reactions that are triggered by fungal infections are being deciphered.

With infectious diseases, it is often not the pathogen itself, but rather an excessive inflammatory immune response (= sepsis) that contributes to the patient’s death, for instance as a result of organ damage. On intensive care units, sepsis is the second-most common cause of death worldwide. In patients with a severely compromised specially, life-threatening candida fungal infections represent a high risk of sepsis.

The working group led by Karl Kuchler in the Christian Doppler Laboratory for Infection Biology (Max. F. Perutz Laboratories at the Vienna Biocenter Campus) has now deciphered the molecular causes of life-threatening inflammatory reactions that are triggered by fungal infections: two highly aggressive types of phagocytes in the immune system (neutrophils and inflammatory monocytes), which however also have a high potential for collateral destruction, mediate the inflammatory reaction during an infection with candida. Certain interferons, the messenger substances used by the immune system, which are excreted during , stimulate the influx of immune cell types to infected organs and lead to sepsis.

Strategy: block the immune response

“We have been able to demonstrate for the first time that the targeted blockade of this immune response with inflammation-inhibiting drugs can significantly reduce candida sepsis and therefore mortality,” says Karl Kuchler, who used an anti-inflammatory substance in the study that is also used as an active ingredient in the treatment of type 2 diabetes – namely pioglitazone.

When this medication was administered, the number and activity of neutrophils and inflammatory monocytes in the mouse model were specifically reduced, and the survival rate was increased for invasive candida infections. “The targeted blockade of excessive immune responses could therefore provide new therapeutic approaches to increase the chances of recovery from life-threatening fungal sepsis,” says Kuchler.

Infectious diseases are the world’s number 1 cause of death, with pathogenic fungi being responsible for extremely dangerous infections. Worldwide, more than € 6 billion are spent each year on anti-fungal medications, and the total costs of the medical treatment of infectious diseases caused by is estimated at hundreds of billions of Euros. 

More information:Type I Interferons Promote Fatal Immunopathology by Regulating Inflammatory Monocytes and Neutrophils during Candida Infections”, Olivia Majer, et al. PLoS Pathog. 2012 June.

add to favorites email to friend print save as pdf

Related Stories

Researchers find quick candida test

Aug 02, 2011

A team led by a Massey University researcher has developed a diagnostic tool that could save the lives of some of the 60 people estimated to die each year in New Zealand from the fungal infection candidemia – and thousands ...

Gamma interferon could aid fight against fungal infections

Oct 31, 2007

Interferon, the “superhero” cure for viral infections, may be a strong weapon in the battle against fungal infections in immunocompromised patients, according to an article in the November issue of Microbiology Today.

Late-stage sepsis suppresses immune system

Jan 11, 2012

(Medical Xpress) -- Patients who die from sepsis are likely to have had suppressed immune systems that left them unable to fight infections, researchers at Washington University School of Medicine in St. Louis ...

Recommended for you

Liberia free of Ebola by Christmas, says president

43 seconds ago

Liberia's president on Monday urged her countrymen to double their efforts to reach the government's goal of having zero new Ebola cases by Dec. 25, a target some experts have described as highly ambitious.

Madagascar working to contain plague outbreak

16 minutes ago

Madagascar said Monday it is trying to contain an outbreak of plague—similar to the Black Death that swept Medieval Europe—that has killed 40 people and is spreading to the capital Antananarivo.

Developing a noninvasive test for endometriosis

19 minutes ago

Researchers at UC San Francisco have identified patterns of genetic activity that can be used to diagnose endometriosis and its severity, a finding that may offer millions of women an alternative to surgery through a simple ...

User comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.